[Minimal change nephrotic syndrome : new insights into disease pathogenesis].
Idiopathic nephrotic syndrome is the most frequent glomerular disease in children. While genetic analyses have provided new insights into disease pathogenesis through the discovery of several podocyte genes mutated in distinct forms of inherited nephrotic syndrome, the molecular bases of minimal change nephrotic syndrome (MCNS) and focal and segmental glomerulosclerosis (FSGS) with relapse remain unclear. Although immune cell disorders, which may involve both innate and adaptive immunity, appear to play a role in the pathogenesis of steroid sensitive MCNS, the mechanisms by which they induce podocyte dysfunction remain unresolved. It was postulated that podocyte injury results from a circulating factor secreted by abnormal T cells, but the possibility that bipolarity of the disease results from a functional disorder shared by both cell systems is not excluded. MCNS relapses are associated with an activation of the immune system, including an expansion of T and B cell compartments and production of growth factors as well as many cytokines. Dysfunction of T cells is supported by three main findings: (1) inhibition of a type III hypersensitivity reaction ; (2) defects in immunoglobulin switch ; (3) unclassical T helper polarization resulting from transcriptional interference between Th1 and Th2 transcriptional factors.
Audard
Vincent
V
Inserm U 841, Institut Mondor de Recherche Biomédicale (IMRB), Département génétique , Equipe 21.
Lang
Philippe
P
Sahali
Dil
D
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002463:Cell Membrane Permeability; D016207:Cytokines / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D034141:Hypoalbuminemia / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000209:etiology; D051076:Proto-Oncogene Proteins c-fyn / Q000502:physiology; D012008:Recurrence
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; C113267:nephrin; D051076:Proto-Oncogene Proteins c-fyn